The hyperphagic effect of the selective melanocortin-4 receptor antagonist HS014 is gender specific.

Abstract

Agouti-related peptide (AgRP) differentially affects food intake and energy expenditure in male and female rats. Because AgRP is non-selective for the MC3 and MC4 receptors, the following study aimed to determine the ability of a selective MC4R antagonist HS014 to increase food intake and energy expenditure in intact and gonadectomized rats. To achieve this, male and female age-matched Long-Evans rats were gonadectomized followed by an intracerebroventricular cannulation 4 weeks later. Two weeks after cannulation rats were injected with saline followed by 1 nmol HS014 a week later. The night before each injection rats were placed into the indirect calorimeter for acclimatization. Rats were injected the following morning in the middle of the light phase after which food intake and energy expenditure were measured for 4 hours. All rats regardless of gonadal status increased food intake following HS014. However, intact males were significantly more sensitive to HS014 compared to intact females (p